The Transgenic Core provides state-of-the-art molecular tools to Project investigators. Centralizing these functions within a single Core derives substantial cost savings and ensures the proper and rigorous use of these approaches. First, numerous lines of transgenic and knockout mice, obtained from other laboratories, are required for the studies proposed in this Center. The Core will be responsible for breeding, genotyping, and maintaining the progeny for use by the individual Projects, as well as providing the appropriate control mice. Second, several new lines of transgenic and knockout mice, required for the Center's Projects, will be made as part of this Core. Among these new lines are those that manipulate the expression of specific genes both temporally and spatially, in other words, inducible and cell-targeted mutations. Our group has significant experience with these methods, which include the tetracycline gene regulation system and the Cre-IoxP system. A major goal of the Core is to now adapt these methods to generate truly inducible, cell-targeted knockouts. Third, the Core will provide Project investigators with herpes simplex viral vectors required for the research. In addition, the Core will work to improve the viral methodologies available, for example, using adeno-associated viral vectors, as well as viral vectors expressing Cre recombinase to induce a highly restricted gene knockout in the brain. Fourth, the Center's Projects utilize DNA microarrays (both glass-based arrays and Affymetrix chips) to study differences in gene expression within the appetitive neural circuits of experimental animals. The Core will provide the arraying and data analysis for Project investigators. By centralizing this activity, we will ensure a high quality of the array data and the ready ability to compare and contrast array findings among the various Projects. Indeed, the array data we've already accumulated have demonstrated common changes in gene expression in mice with mutations in the various proteins of interest to the six Projects.